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Ji-Feng Feng,1 Jian-Ming Zhao,2 Xun Yang,1 Liang Wang1 1Department of Thoracic Oncological Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Thoracic Surgery, Jinhua Guangfu Hospital, Jinghua, Zhejiang Province, People’s Republic of ChinaCorrespondence: Ji-Feng Feng; Liang Wang Email fengjif@163.com; drwang_liang@126.comBackground: Esophageal basaloid squamous cell carcinoma (EBSCC) is a rare malignancy. Serum apolipoprotein A-I (APO A-I) has proved to be a potentially useful prognostic indicator in various cancers. However, no studies have analyzed the prognostic significance of serum APO A-I in patients with EBSCC. The aim of this study was to investigate the prognostic impact of preoperative serum APO A-I in patients with EBSCC.Methods: Between 2007 and 2018, a retrospective study of 4050 patients with resectable esophageal squamous cell carcinoma (ESCC) including the levels of preoperative serum lipids was conducted and evaluated. The best cut-off values of the preoperative serum lipids were evaluated by receiver operating characteristic (ROC) curves. Kaplan–Meier analyses and Cox regression analyses were analyzed the overall survival (OS) and recurrence-free survival (RFS). A prediction model of nomogram was developed to predict individual OS and RFS in EBSCC.Results: There were 53 patients enrolled in the study, which accounted for 1.31% (53/4050) of all primary ESCC. The best cut-off point was 1.305 g/L for serum APO A-I according to the ROC curve. Patients with lower levels of serum preoperative APO A-I were associated with worse RFS (16.1% vs 54.5%, P = 0.006) and OS (29.0% vs 63.6%, P = 0.010). The results indicated that serum APO A-I serves as an independent predictor in patients with EBSCC regarding OS [hazard ratio (HR): 0.352; 95% confidence interval (CI): 0.154– 0.808; P = 0.014] and RFS (HR: 0.397; 95% CI: 0.185– 0.850; P = 0.017).Conclusion: Preoperative serum APO A-I is an independent predictor regarding OS and RFS in EBSCC. As far as we know, this is the first study in EBSCC to explore the serum APO A-I in patients with EBSCC.Keywords: esophageal basaloid squamous cell carcinoma, EBSCC, apolipoprotein A-I, APO A-I, recurrence-free survival, RFS, overall survival, OS, prognosis

Ji-Feng Feng,1,2 Jian-Ming Zhao,3 Sheng Chen,1 Qi-Xun Chen1,2 1Department of Thoracic Oncological Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, People’s Republic of China; 2Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, 310022, People’s Republic of China; 3Department of Thoracic Surgery, Jinhua Guangfu Hospital, Jinghua, 321001, People’s Republic of ChinaCorrespondence: Ji-Feng FengDepartment of Thoracic Oncological Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, No. 38 Guangji Road, Hangzhou, 310022, People’s Republic of ChinaEmail Fengjf@zjcc.org.cnBackground: The lung immune prognostic index (LIPI), a novel index combined with serum lactate dehydrogenase (LDH) and derived neutrophil to lymphocyte ratio (dNLR), is recently proposed to predict prognosis in lung cancer. The LIPI is not a unique indicator for lung cancer. However, the prognostic role of LIPI has not yet been evaluated in extra-pulmonary cancer. The aim of this study was to determine whether LIPI is still a useful prognostic indicator for patients with resected esophageal squamous cell carcinoma (ESCC).Methods: The clinical data including preoperative laboratory results for 361 consecutive resected ESCC cases from 2007 to 2010 were retrospectively analyzed. A LIPI based on serum LDH and dNLR was conducted, characterizing into 3 groups (LIPI 0, 1 and 2). The association between LIPI and cancer-specific survival (CSS) was analyzed according to the Kaplan–Meier method and Cox regression analysis with hazard ratio (HR) and 95% confidence interval (CI). A nomogram model was conducted by R 3.6.0 software.Results: In this study, 220 (60.9%), 100 (27.7%) and 41 (11.4%) patients had a LIPI of 0, 1 and 2, respectively. The 5-year CSS for LIPI 0, 1 and 2 was 40.9%, 19.0% and 9.8%, respectively (P< 0.001). Subgroup analysis based on TNM stage revealed that HALP was also significantly related to CSS in any stage (TNM I: P=0.002; TNM II: P=0.009; TNM III: P=0.031). The LIPI serves as an independent predictor regarding CSS in multivariate analyses in patients with resected ESCC. Compared to LIPI 0, LIPI 1 and 2 had an HR of 1.419 (95% CI: 1.063– 1.895, P=0.018) and 2.064 (95% CI: 1.403– 3.036, P< 0.001) regarding CSS, respectively. A nomogram was also developed in individualized CSS prediction based on LIPI in patients with resected ESCC.Conclusion: To the best of our knowledge, the present study is the first study to explore the association between LIPI and prognosis in patients with extra-pulmonary cancer. The LIPI, combined with LDH and dNLR, is still a potential independent prognostic marker in patients with resected ESCC.Keywords: esophageal squamous cell carcinoma, lung immune prognostic index, lactate dehydrogenase, derived neutrophil to lymphocyte ratio, prognosis

Ru-Yin Hu,1–3,* Xiao-Bin Tian,3,* Bo Li,3 Rui Luo,3 Bin Zhang,3 Jin-Min Zhao1 1Department of Orthopaedics, Guangxi Medical University, Nanning 530021, People’s Republic of China; 2Department of Orthopaedics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, People’s Republic of China; 3Department of Orthopaedics, Guizhou Provincial People’s Hospital, Guiyang 550002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jin-Min ZhaoDepartment of Orthopaedics, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, Guangxi 530021, People’s Republic of ChinaTel +86 771 13985048001Email zhao948586007@126.comBackground: Existing drugs are far from enough for investigators and patients to administrate the therapy of rheumatoid arthritis. Drug repositioning has drawn broad attention by reusing marketed drugs and clinical candidates for new uses.Purpose: This study attempted to predict candidate drugs for rheumatoid arthritis treatment by mining the similarities of pathway aberrance induced by disease and various drugs, on a personalized or customized basis.Methods: We firstly measured the individualized pathway aberrance induced by rheumatoid arthritis based on the microarray data and various drugs from CMap database, respectively. Then, the similarities of pathway aberrances between RA and various drugs were calculated using a Kolmogorov–Smirnov weighted enrichment score algorithm.Results: Using this method, we identified 4 crucial pathways involved in rheumatoid arthritis development and predicted 9 underlying candidate drugs for rheumatoid arthritis treatment. Some candidates with current indications to treat other diseases might be repurposed to treat rheumatoid arthritis and complement the drug group for rheumatoid arthritis.Conclusion: This study predicts candidate drugs for rheumatoid arthritis treatment through mining the similarities of pathway aberrance induced by disease and various drugs, on a personalized or customized basis. Our framework will provide novel insights in personalized drug discovery for rheumatoid arthritis and contribute to the future application of custom therapeutic decisions.Keywords: rheumatoid arthritis, drug repositioning, individualized pathway aberrance, differential pathway

Colorectal cancer is one of the most common cancers. Survivin is strongly immunogenic in a fraction of colorectal cancer patients. The present study was designed to determine whether full-length mouse Survivin dominant-negative mutant SurvivinT34A has the antitumor activity in a murine colon carcinoma model. The complex of cationic liposome (DOTAP/Chol) to plasmid pORF9-mSurvivin T34A was administered intravenously in a mouse subcutaneous (S. C.) CT 26 tumor model. Apoptotic cells and anti-angiogenesis were evaluated by fluorescent in situ TUNEL assay and by immunohistochemistry with an antibody reactive to CD31, respectively. A 4 h 51Cr release assay was performed to determine Survivin-specific cytotoxicity. The adoptive transfer of CD8+ or CD4+ T-lymphocytes assay was to further explore the roles of immune cell subsets. We demonstrated the complex of cationic liposome (DOTAP/Chol) to plasmid pORF9--mSurvivin T34A when administered intravenously induced an efficient antitumor activity in a S. C. CT26 tumor model in mice. The main mechanism is involved in three aspects: triggering the apoptosis of tumor cells, inhibiting angiogenesis, and inducing Survivin-specific immune response. Our observations may have potential implications for the further exploration of the treatment of human colorectal cancer by intravenous delivery of dominant-negative mutant Survivin T34A. [ABSTRACT FROM AUTHOR]

With an aging population seeking infertility treatment, diminished ovarian reserve (DOR) is a prevalent indication for assisted reproductive technology (ART). This study aims to investigate the relationship between sleep parameters and DOR among women attending an infertility clinic. Methods We consecutively enrolled women attending an infertility clinic from July 2020 to June 2021. Participants completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale(ESS), and STOP-Bang Questionnaire to assess self-reported sleep quality. DOR-related indices including antral follicle count, anti-Müllerian hormone(AMH), follicle-stimulating hormone (FSH) were evaluated. A total of 979 women were enrolled, with 148 classified into the DOR group and 831 in the non-DOR group. The DOR group was notably older compared to the non-DOR group. Analysis showed that the DOR group exhibited significantly shorter sleep onset latency (p = 0.001) and shorter total sleep duration (p = 0.014) compared to the non-DOR group. Logistic regression analysis identified age, PSQI-sleep latency, and PSQI score as independent factors associated with an increased risk of DOR(all p < 0.05). Furthermore, stratified analysis by age group revealed that snoring and PSQI-sleep latency were particularly notable risk factors for DOR among women aged 35 years and older (OR = 2.489, p = 0.040; OR = 2.007, p = 0.008, respectively). Our study highlights that shorter sleep onset latency and shorter total sleep duration may be associated with DOR among women undergoing ART treatments. Particularly noteworthy, snoring and sleep latency were identified as additional risk factors for DOR among women aged 35 years and older., (© 2024. The Author(s).)

The present article introduced an natural enzyme-covered/amino-modified Pd-Pt bimetallic-doped zeolitic imidazolate framework (NAPPZ) for ultrasensitive and specific detection of glucose. The dodecahedral nanomaterial zeolitic imidazolate framework (ZIF-8)-loaded Pd-Pt bimetallic nanoparticles endowed the composite with peroxidase-like activity. The modification with glucose oxidase (GOx) facilitated the rapid access of H 2 O 2 produced through glucose oxidation to the Pd-Pt nanoparticles vicinity reducing diffusion. GOx specifically catalyzes the transformation of glucose into H 2 O 2 , which then H 2 O 2 rapidly migrates to the Pd-Pt nanoparticles, catalyzing the oxidation of colorless o-phenylenediamine into the orange-yellow product 2,3-diaminophenazine. Based on the aforementioned cascade reaction, the NAPPZ and NAPPZ based on ChOx were utilized for detecting glucose in human urine samples and cholesterol in milk, respectively. The NAPPZ strategy presented a broad detection range (20-1100 μmol L -1 ) and a low detection limit (15.9 μmol L -1 ) for glucose, and the NAPPZ based on ChOx strategy approach offered a broad detection range (10-500 μmol L -1 ) and low detection limit (6.4 μmol L -1 ) for cholesterol. Therefore, this novel method holds significant potential in the areas of clinical diagnostics and food safety., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Hen egg low-density lipoprotein (heLDL), as alternative of serum-derived LDL, was used as drug delivery system of ceftiofur (CEF). The CEF-loaded hen egg low-density lipoprotein (CEF-heLDL) with complete apolipoprotein structure and high drug loading rate was synthesized, possesses suitable particle size. CEF-heLDL undergoes cellular uptake and colocalizes with lysosomes in vitro. An intracellular infection model of the bovine endometrial epithelial cells and a coeliac-induced inflammation model of mice by Staphylococcus aureus (S. aureus) were established, and significantly lower intracellular S. aureus levels of CEF-heLDL group than CEF-free group (P < 0.001) was observed. The antibacterial efficacy was sustained for 24 h. Up to 400 mg/kg of CEF-heLDL, 20 times the clinical practice, were intraperitoneally administrated, and no significant toxicity signs on mice were observed. HeLDLs is an effective, safe, and cheap drug carrier, and could also be used for transmembrane delivering other antibiotics., Competing Interests: Declaration of competing interest CJS, MW, BYT, ZSY, LB, YJL, HYL, HSSR, LPF, WYF, and Gll are co-inventors on a patent application for a fusion method for yolk low-density lipoprotein and ceftiofur, which is available for licensing. The other authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Exploiting high-performance magnetic beads for specific enrichment of ribonucleic acid (RNA) has important significance in the biomedical research field. Herein, a simple strategy was proposed for fabricating boronate-decorated polyethyleneimine-grafted magnetic agarose beads (BPMAB), which can selectively isolate cis-diol-containing substances through boronate affinity. The size of the basic magnetic agarose beads was controlled through the emulsification of the water-in-oil emulsion with a high-speed shear machine, which enhanced the specific surface area of BPMAB. Subsequently, to modify more boronic acid ligands, branched PEI with excellent hydrophilicity and numerous reaction sites was grafted. 2,4-Difluoro-3-formylphenyl boronic acid (2,4-DFPBA) was covalently immobilized for selectively capturing cis-diol-containing substances under physiological condition (pH 7.4). The BPMAB with a diameter range from 1.86 μm to 11.60 μm possessed clearly spherical structure, and excellent magnetic responsiveness and suspension ability in aqueous solution. β-Nicotinamide adenine dinucleotide (β-NAD), a short-chain cis-diol carrying agent, was selected as a target molecule for evaluating the adsorption property of BPMAB and the maximum adsorption capacity of BPMAB for β-NAD could reach 205.11 mg g -1 . In addition, the BPMAB as adsorbent was used to selectively enrich RNA from mammalian cells. The maximum adsorption capacity of BPMAB for RNA was 140.50 mg g -1 . Under optimized conditions, the BPMAB-based MSPE successfully enriched the high-quality total RNA with 28S to 18S ribosomal RNA ratios ranging from 2.06 to 2.16. According to the PCR analysis of GADPH gene, the extracted total RNA was successfully reverse transcribed into cDNA. Therefore, we believe that the BPMAB-based MSPE could be applicable for the specific enrichment of RNA from complex biological systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide, and metastasis is the main cause of early recurrence and poor prognosis. However, the mechanism of metastasis remains poorly understood., Aim: To determine the possible mechanism affecting HCC metastasis and provide a possible theoretical basis for HCC treatment., Methods: The candidate molecule lecithin-cholesterol acyltransferase (LCAT) was screened by gene microarray and bioinformatics analysis. The expression levels of LCAT in clinical cohort samples was detected by quantitative real-time polymerase chain reaction and western blotting. The proliferation, migration, invasion and tumor-forming ability were measured by Cell Counting Kit-8, Transwell cell migration, invasion, and clonal formation assays, respectively. Tumor formation was detected in nude mice after LCAT gene knockdown or overexpression. The immunohistochemistry for Ki67, E-cadherin, N-cadherin, matrix metalloproteinase 9 and vascular endothelial growth factor were performed in liver tissues to assess the effect of LCAT on HCC. Gene set enrichment analysis (GSEA) on various gene signatures were analyzed with GSEA version 3.0. Three machine-learning algorithms (random forest, support vector machine, and logistic regression) were applied to predict HCC metastasis in The Cancer Genome Atlas and GEO databases., Results: LCAT was identified as a novel gene relating to HCC metastasis by using gene microarray in HCC tissues. LCAT was significantly downregulated in HCC tissues, which is correlated with recurrence, metastasis and poor outcome of HCC patients. Functional analysis indicated that LCAT inhibited HCC cell proliferation, migration and invasion both in vitro and in vivo . Clinicopathological data showed that LCAT was negatively associated with HCC size and metastasis (HCC size ≤ 3 cm vs 3-9 cm, P < 0.001; 3-9 cm vs > 9 cm, P < 0.01; metastatic-free HCC vs extrahepatic metastatic HCC, P < 0.05). LCAT suppressed the growth, migration and invasion of HCC cell lines via PI3K/AKT/mTOR signaling. Our results indicated that the logistic regression model based on LCAT, TNM stage and the serum level of α-fetoprotein in HCC patients could effectively predict high metastatic risk HCC patients., Conclusion: LCAT is downregulated at translational and protein levels in HCC and might inhibit tumor metastasis via attenuating PI3K/AKT/mTOR signaling. LCAT is a prognostic marker and potential therapeutic target for HCC., Competing Interests: Conflict-of-interest statement: The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The extent of intrahepatic infiltration of perihilar cholangiocarcinoma (PHCC) remains unclear. This research aimed to explore the pattern and extent of intrahepatic infiltration of PHCC to guide surgical treatment and pathological research., Materials and Methods: This study included 62 patients diagnosed with PHCC who underwent major hepatectomy. A whole-mount digital liver pathology system (WDLPS) for hepatectomy specimens greater than 10 × 10 cm was used to panoramically assess the intrahepatic infiltration extent of PHCC., Results: The distal intrahepatic infiltration (DIHI) and radial liver invasion (RLI) were important parts of intrahepatic infiltration for PHCC explored by WDLPS. The study confirmed that 75.8% of PHCCs had RLI and the infiltration distance in all patients were within 15,000 µm, 62.9% of PHCCs had DIHI greater than 1 cm away from the main tumor in liver parenchyma. The recurrence-free survival rates and overall survival rates of patients with DIHI were poorer than the patients without DIHI (P＜0.0001, P=0.0038). Arterial invasion on the resected side could be an excellent predictor. A total of 105 liver lobes were resected from 62 PHCC patients. The invasion rates of the left lateral, left medial, right anterior, and right posterior lobe of PHCC were 79%, 100, 100%, and 69% respectively., Conclusion: The presence of DIHI in most PHCCs was a significant predictor of poor postoperative recurrence and survival. Based on the extent of intrahepatic infiltration, minor hepatectomy was not suitable as the curative surgery for PHCC. Major hepatectomy and liver transplantation were the ideal radical treatment., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Bacterial infections already pose a significant threat to skin wounds, especially in diabetic patients who have difficulty healing wounds. However, wound or bacterial infections are known to produce excess reactive oxygen species (ROS), and hypoxia may further hinder wound healing and the development of chronic wounds. In this study, a multifunctional hydrogel for ROS scavenging and bacterial inhibition was developed by cross-linking polyvinyl alcohol (PVA) and sodium alginate (SA) with graphene oxide (GO) loaded with silver-platinum hybrid nanoparticles (GO@Ag-Pt). The PVA/SA hydrogel loaded with GO@Ag-Pt exhibited the ability to scavenge different types of ROS, generate O 2 , and kill a broad spectrum of bacteria in vitro. The silver-platinum hybrid nanoparticles significantly increased the antibacterial ability against Escherichia coli and Staphylococcus aureus compared with silver nanoparticles (AgNps). GO@Ag-Pt loaded hydrogel was effective in treating infections caused by S.aureus, thereby significantly promoting wound healing during the inflammatory phase. Hydrogel therapy significantly reduced the level of ROS and alleviated inflammation levels. Notably, our ROS-scavenging, antibacterial hydrogels can be used to effectively treat various types of wounds, including difficult-to-heal diabetic wounds with bacterial infections. Thus, this study proposes an effective strategy for various chronic wound healing based on ROS clearance and bacteriostatic hydrogels., (© 2024 Wiley Periodicals LLC.)

Background: The optimal approach for managing hepatic hemangioma is controversial., Aim: To evaluate a clinical grading system for management of hepatic hemangioma based on our 17-year of single institution experience., Methods: A clinical grading system was retrospectively applied to 1171 patients with hepatic hemangioma from January 2002 to December 2018. Patients were classified into four groups based on the clinical grading system and treatment: (1) Observation group with score < 4 (Obs score < 4); (2) Surgical group with score < 4 (Sur score < 4); (3) Observation group with score ≥ 4 (Obs score ≥ 4); and (4) Surgical group with score ≥ 4 (Sur score ≥ 4). The clinico-pathological index and outcomes were evaluated., Results: There were significantly fewer symptomatic patients in surgical groups (Sur score ≥ 4 vs Obs score ≥ 4, P < 0.001; Sur score < 4 vs Obs score < 4, χ ² = 8.60, P = 0.004; Sur score ≥ 4 vs Obs score < 4, P < 0.001). The patients in Sur score ≥ 4 had a lower rate of in need for intervention and total patients with adverse event than in Obs score ≥ 4 ( P < 0.001; P < 0.001). Nevertheless, there was no significant difference in need for intervention and total patients with adverse event between the Sur score < 4 and Obs score < 4 ( P > 0.05; χ ² = 1.68, P > 0.05)., Conclusion: This clinical grading system appeared as a practical tool for hepatic hemangioma. Surgery can be suggested for patients with a score ≥ 4. For those with < 4, follow-up should be proposed., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Dopamine axons are the only axons known to grow during adolescence. Here, using rodent models, we examined how two proteins, Netrin-1 and its receptor, UNC5C, guide dopamine axons toward the prefrontal cortex and shape behaviour. We demonstrate in mice ( Mus musculus ) that dopamine axons reach the cortex through a transient gradient of Netrin-1-expressing cells - disrupting this gradient reroutes axons away from their target. Using a seasonal model (Siberian hamsters; Phodopus sungorus ) we find that mesocortical dopamine development can be regulated by a natural environmental cue (daylength) in a sexually dimorphic manner - delayed in males, but advanced in females. The timings of dopamine axon growth and UNC5C expression are always phase-locked. Adolescence is an ill-defined, transitional period; we pinpoint neurodevelopmental markers underlying this period., Competing Interests: DH, RK, SS, DM, RA, EE, AH, TO, AD, CP, JZ, KS, LL, QC, GL, MP, CF No competing interests declared, (© 2023, Hoops et al.)

Microvascular invasion (MVI) is an adverse prognostic indicator of tumor recurrence after surgery for hepatocellular carcinoma (HCC). Therefore, developing a nomogram for estimating the presence of MVI before liver resection is necessary. We retrospectively included 260 patients with pathologically confirmed HCC at the Fifth Medical Center of Chinese PLA General Hospital between January 2021 and April 2024. The patients were randomly divided into a training cohort (n = 182) for nomogram development, and a validation cohort (n = 78) to confirm the performance of the model (7:3 ratio). Significant clinical variables associated with MVI were then incorporated into the predictive nomogram using both univariate and multivariate logistic analyses. The predictive performance of the nomogram was assessed based on its discrimination, calibration, and clinical utility. Serum carnosine dipeptidase 1 ([CNDP1] OR 2.973; 95 % CI 1.167-7.575; p = 0.022), cirrhosis (OR 8.911; 95 % CI 1.922-41.318; p = 0.005), multiple tumors (OR 4.095; 95 % CI 1.374-12.205; p = 0.011), and tumor diameter ≥3 cm (OR 4.408; 95 % CI 1.780-10.919; p = 0.001) were independent predictors of MVI. Performance of the nomogram based on serum CNDP1, cirrhosis, number of tumors and tumor diameter was achieved with a concordance index of 0.833 (95 % CI 0.771-0.894) and 0.821 (95 % CI 0.720-0.922) in the training and validation cohorts, respectively. It fitted well in the calibration curves, and the decision curve analysis further confirmed its clinical usefulness. The nomogram, incorporating significant clinical variables and imaging features, successfully predicted the personalized risk of MVI in HCC preoperatively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Carnosine dipeptidase 1 (CNDP1), an enzyme integral to the hydrolysis of dipeptides containing histidine, plays an indispensable role in myriad physiological processes, including hydrolysis of proteins, maturation of specific biochemical functionalities within proteins, tissue regeneration, and regulation of cell cycle. However, the implications of CNDP1 in oncogenesis and its prognostic value are not yet fully elucidated. Initially, we procured the GSE40367 dataset from the Gene Expression Omnibus and established a protein-protein interaction network. Thereafter, we conducted functional and pathway enrichment analyses utilizing GO, KEGG, and GSEA. Moreover, we undertook an association analysis concerning the expression of CNDP1 with immune infiltration, along with survival analysis across various cancers and specifically in hepatocellular carcinoma (HCC). Our study uncovered a total of 2,248 differentially expressed genes, with a down-regulation of CNDP1 in HCC and other cancers. Our explorations into the relationship between CNDP1 and immune infiltration disclosed a negative correlation between CNDP1 expression and the presence of immune cells in HCC. Survival analyses revealed that diminished expression of CNDP1 correlates with an adverse prognosis in HCC and several other types of cancer. These observations intimate that CNDP1 holds promise as a novel prognostic biomarker for both pan-cancer and HCC., Competing Interests: Conflict of interest: The authors declare that they have no conflict of interest., (© 2024 the author(s), published by De Gruyter.)

Cytotoxicity assays are crucial for assessing the efficacy of drugs in killing cancer cells and determining their potential therapeutic value. Measurement of the effect of drug concentration, which is an influence factor on cytotoxicity, is of great importance. This paper proposes a cytotoxicity assay using microwave sensors in an end-point approach based on the detection of the number of live cells for the first time. In contrast to optical methods like fluorescent labeling, this research uses a resonator-type microwave biosensor to evaluate the effects of drug concentrations on cytotoxicity by monitoring electrical parameter changes due to varying cell densities. Initially, the feasibility of treating cells with ultrapure water for cell counting by a microwave biosensor is confirmed. Subsequently, inhibition curves generated by both the CCK-8 method and the new microwave biosensor for various drug concentrations were compared and found to be congruent. This agreement supports the potential of microwave-based methods to quantify cell growth inhibition by drug concentrations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Wang, Shi, Wang, Jiang, Yang, Gao and Qiang.)

This study presents a biosensor fabricated based on integrated passive device (IPD) technology to measure microbial growth on solid media in real-time. Yeast ( Pichia pastoris , strain GS115) is used as a model organism to demonstrate biosensor performance. The biosensor comprises an interdigital capacitor in the center with a helical inductive structure surrounding it. Additionally, 12 air bridges are added to the capacitor to increase the strength of the electric field radiated by the biosensor at the same height. Feasibility is verified by using a capacitive biosensor, and the change in capacitance values during the capacitance detection process with the growth of yeast indicates that the growth of yeast can induce changes in electrical parameters. The proposed IPD-based biosensor is used to measure yeast drop-added on a 3 mm medium for 100 h at an operating frequency of 1.84 GHz. The resonant amplitude of the biosensor varies continuously from 24 to 72 h due to the change in colony height during vertical growth of the yeast, with a maximum change of 0.21 dB. The overall measurement results also fit well with the Gompertz curve. The change in resonant amplitude between 24 and 72 h is then analyzed and reveals a linear relationship with time with a coefficient of determination of 0.9844, indicating that the biosensor is suitable for monitoring yeast growth. Thus, the proposed biosensor is proved to have potential in the field of microbial proliferation detection.

Since different quantities of white blood cells (WBCs) in solution possess an adaptive osmotic pressure of cells, the WBCs themselves and in solution have similar concentrations, resulting in them having similar dielectric properties. Therefore, a microwave sensor could have difficulty in sensing the quantity variation when WBCs are in solution. This paper presents a highly sensitive, linear permittivity-inspired microwave biosensor for WBCs, counting through the evaporation method. Such a measurement method is proposed to record measurements after the cell solution is dripped onto the chip and is completely evaporated naturally. The proposed biosensor consists of an air-bridged asymmetric differential inductor and a centrally located circular fork-finger capacitor fabricated on a GaAs substrate using integrated passive fabrication technology. It is optimized to feature a larger sensitive area and improved Q-factor, which increases the effective area of interaction between cells and the electromagnetic field and facilitates the detection of their changes in number. The sensing relies on the dielectric properties of the cells and the change in the dielectric constant for different concentrations, and the change in resonance properties, which mainly represents the frequency shift, corresponds to the macroscopic change in the concentration of the cells. The microwave biosensors are used to measure biological samples with concentrations ranging from 0.25 × 10 6 to 8 × 10 6 cells per mL in a temperature (26.00 ± 0.40 °C) and humidity (54.40 ± 3.90 RH%) environment. The measurement results show a high sensitivity of 25.06 Hz/cells·mL -1 with a highly linear response of r 2 = 0.99748. In addition, a mathematical modeling of individual cells in suspension is performed to estimate the dielectric constant of individual cells and further explain the working mechanism of the proposed microwave biosensor.

Background: Type 1 diabetes is believed to be an autoimmune condition, characterized by destruction of insulin-producing cells, due to the detrimental inflammation in pancreas. Growing evidences have indicated the important role of type I interferon in the development of type 1 diabetes., Methods: Trex1-deficient rats were generated by using CRISPR-Cas9. The fasting blood glucose level of rat was measured by a Roche Accuchek blood glucose monitor. The levels of insulin, islet autoantibodies, and interferon-β were measured using enzyme-linked immunosorbent assay. The inflammatory genes were detected by quantitative PCR and RNA-seq. Hematein-eosin staining was used to detect the pathological changes in pancreas, eye and kidney. The pathological features of kidney were also detected by Masson trichrome and periodic acid-Schiff staining. The distribution of islet cells, immune cells or ssDNA in pancreas was analyzed by immunofluorescent staining., Results: In this study, we established a Trex1-deletion Sprague Dawley rat model, and unexpectedly, we found that the Trex1 -/- rats spontaneously develop type 1 diabetes. Similar to human diabetes, the hyperglycemia in rats is accompanied by diabetic complications such as diabetic nephropathy and cataract. Mechanistical investigation revealed the accumulation of ssDNA and the excessive production of proinflammatory cytokines, including IFN-β, in Trex1 null pancreas. These are likely contributing to the inflammation in pancreas and eventually leading to the decline of pancreatic β cells., Conclusions: Our study links the DNA-induced chronic inflammation to the pathogenesis of type 1 diabetes, and also provides an animal model for type 1 diabetes studies., (© 2023. The Author(s).)

Intrahepatic cholangiocarcinoma (iCCA) can originate from the large bile duct group (segment bile ducts and area bile ducts), small bile duct group (septal bile ducts and interlobular bile ducts), and terminal bile duct group (bile ductules and canals of Hering) of the intrahepatic biliary tree, which can be histopathological corresponding to large duct type iCCA, small duct type iCCA and iCCA with ductal plate malformation pattern, and cholangiolocarcinoma, respectively. The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies, tissue structures, growth patterns, invasive behaviors, immunophenotypes, molecular mutations, and surgical prognoses. For these reasons, this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA, mainly based on the 5 th edition of the World Health Organization Classification of Tumours of the Digestive System., Competing Interests: The authors have no conflict of interests related to this publication., (© 2023 Authors.)

Grading seeds based on grain size is an effective measure to improve population regularity degree and increase the yield of summer maize. Taking Denghai 605 as the experimental material, we set up a field experiment with treatments based on grain size: large seeds (L), medium-round seeds (MR), medium-flat seeds (MF), medium-round and medium-flat mixed seeds (MRF), and small seeds (S), with no-grading seeds as control (CK). We investigated seedling emergence rate, population regularity degree (including height, ear height and stem diameter), seedling sturdiness index, photosynthetic characteristics, dry matter accumulation and distribution characteristics, and yield. The results showed that the emergence rate followed an order of L>MR>MRF>MF>CK>S, with that of L treatment differed little from MR, MF and MRF treatments, but being significantly higher than S and CK treatments. Plant height and stem diameter population regularity degree of MRF treatment before seven-leaf stage was not different from those of L, MR, MF and S treatments, but significantly higher than those of CK. At the tasseling stage, all treatments had higher population regularity degree of plant height than other stages. Ear height population regularity degree of L, MR, MF, MRF, and S increased by 11.1%, 10.3%, 9.5%, 7.1%, and 6.4% compared with CK, respectively. The seedling sturdiness index of MRF treatment increased by 36.7% compared with S treatment, but was not significantly different from L treatment. The leaf area index of the L and MRF treatments was significantly higher than that of CK, and both had higher population photosynthetic properties. The population dry matter accumulation showed a pattern as L>MR>MRF>MF>CK>S. There was no significant difference among L, MR, and MRF treatments, but that in L being obviously higher than MF, CK, and S treatments. After seed grading, the number of harvested ears of the L and MRF treatments increased significantly, and the yield were shown as L>MR>MRF>MF>CK>S. There was no difference between the yield of MRF, MR and MF treatments. In conclusion, the performance of L treatment was improved but the number was small. Considering the grading cost and yield, the MRF treatment can save the seed amounts of sowing, realize mechanized sowing and precision sowing.

Liver fibrosis (LF) is an important reparative process in response to acute or chronic hepatic injury, which has the potential to advance towards cirrhosis and hepatocellular carcinoma. Dietary naringin consumption contributes to protection against LF in animal studies, while the exact protective mechanism of naringin remains unclear. This study aimed to investigate the molecular mechanisms behind the potential protective effect of naringin against TAA-induced LF in zebrafish. In this study, we utilized zebrafish to create the LF model and investigate the therapeutic mechanism of naringin. Firstly, we evaluated the changes in hepatic fibrosis and lipid accumulation in the liver following naringin treatment with oil red O, Nile red, and Sirius red and immunohistochemistry. In addition, we employed an ROS probe to directly measure oxidative stress and monitor inflammatory cell migration in a zebrafish transgenic line. Morpholino was used in the knockdown of IDO1 in order to verify its vital role in LF. Our findings demonstrated that naringin exhibited anti-inflammatory and anti-fibrotic action in conjunction with a reversal in lipid accumulation, oxidative stress and suppression of macrophage infiltration and activation of hepatic stellate cells. Furthermore, the results showed that the antifibrotic effect of naringin was removed upon IDO1 knockdown, proving that naringin exerts a protective effect by regulating IDO1. Naringin demonstrates remarkable protective effects against LF, effectively counteracting inflammation and hepatic steatosis in zebrafish liver. These findings suggest that naringin may function as an effective IDO1 inhibitor, holding the potential for clinical translation as a therapeutic agent for the treatment of LF.

Background: Autophagy plays a critical role in the progression of osteoarthritis (OA), mainly by regulating inflammatory and immune responses. However, the underlying mechanisms remain unclear. This study aimed to investigate the potential relevance of autophagy-related genes (ARGs) associated with infiltrating immune cells in OA., Methods: GSE114007, GSE169077, and ARGs were obtained from the Gene Expression Omnibus (GEO) database and the Human Autophagy database. R software was used to identify the differentially expressed autophagy-related genes (DEARGs) in OA. Functional enrichment and protein-protein interaction (PPI) analyses were performed to explore the role of DEARGs in OA cartilage, and then Cytoscape was utilized to screen hub ARGs. Single-sample gene set enrichment analysis (ssGSEA) was used to conduct immune infiltration analysis and evaluate the potential correlation of key ARGs and immune cell infiltration. Then, the expression levels of hub ARGs in OA were further verified by the GSE169077 and qRT-PCR. Finally, Western blotting and immunohistochemistry were used to validate the final hub ARGs., Results: A total of 24 downregulated genes and five upregulated genes were identified, and these genes were enriched in autophagy, mitophagy, and inflammation-related pathways. The intersection results identified nine hub genes, namely, CDKN1A, DDIT3, FOS, VEGFA, RELA, MAP1LC3B, MYC, HSPA5, and HSPA8. GSE169077 and qRT-PCR validation results showed that only four genes, CDKN1A, DDT3, MAP1LC3B, and MYC, were consistent with the bioinformatics analysis results. Western blotting and immunohistochemical (IHC) showed that the expression of these four genes was significantly downregulated in the OA group, which is consistent with the qPCR results. Immune infiltration correlation analysis indicated that DDIT3 was negatively correlated with immature dendritic cells in OA, and FOS was positively correlated with eosinophils., Conclusion: CDKN1A, DDIT3, MAP1LC3B, and MYC were identified as ARGs that were closely associated with immune infiltration in OA cartilage. Among them, DDIT3 showed a strong negative correlation with immature dendritic cells. This study found that the interaction between ARGs and immune cell infiltration may play a crucial role in the pathogenesis of OA; however, the specific interaction mechanism needs further research to be clarified. This study provides new insights to further understand the molecular mechanisms of immunity involved in the process of OA by autophagy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Qin, Zhang, Wu, Ru, Zhong, Zhao and Lan.)

Background: Nonalcoholic fatty liver disease (NAFLD) is associated with disordered lipid and iron metabolism. Our previous study has substantiated the pivotal role of Caveolin-1 (Cav-1) in protecting hepatocytes and mediating iron metabolism in the liver. This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFLD., Methods: Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this study. Cav-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in vitro. Moreover, a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro, respectively, while a high-iron diet was used to construct an in vivo iron overload model. Besides, iron concentration, the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit, Prussian blue staining, Western blotting, immunofluorescence staining, immunohistochemical staining and ELISA. The related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and staining., Results: Significant disorder of lipid and iron metabolism occurred in NAFLD. The expression of Cav-1 was decreased in NAFLD hepatocytes (P < 0.05), accompanied by iron metabolism disorder. Cav-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD, subsequently alleviating the oxidative stress induced by excess ferrous ions in the liver. Further, CD68 + CD163 + macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver, which was contrary to the effect of Cav-1 in hepatocytes. Positive correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers (P < 0.05)., Conclusions: These findings confirm that Cav-1 is an essential target protein that regulates iron and lipid metabolic homeostasis. It is a pivotal molecule for predicting and protecting against the development of NAFLD., (© 2023. The Author(s).)

Developing high-performance magnetic particles for the effective separation and purification of target proteins has become an important topic in the area of biomedical research. In this work, a simple and novel strategy was proposed for fabricating magnetic Fe3O4@agarose-iminodiacetic acid-Ni microspheres (MAIN), which can efficiently and selectively isolate histidine-tagged/rich proteins (His-proteins). Based on the thermoreversible sol-gel transition of agarose, basic magnetic agarose microspheres were prepared through the inverse emulsion method, in which the emulsion contained agarose and amine-modified Fe 3 O 4 nanoparticles. The size of the emulsion was controlled by the emulsification of a high-speed shear machine, which improved the specific surface area of MAIN. Subsequently, the amine-modified Fe 3 O 4 nanoparticles were covalently crosslinked with agarose through epichlorohydrin, which could avoid leakage of the magnetic source during use and increase the stability of MAIN. The microsized MAIN exhibited a clearly visible spherical core-shell structure with a diameter range from 3.4 μm to 9.8 μm, and excellent suspension ability in aqueous solution. The maximum adsorption capacity of MAIN for histidine-rich bovine hemoglobin was 1069.2 mg g -1 at 35 °C, which was higher than those of commercialized and most reported magnetic agarose microspheres/nanoparticles. The MAIN showed excellent adsorption ability and selectivity toward His-proteins in a mixture of histidine-rich bovine serum albumin (BSA) and histidine-poor lysozyme (LYZ). When the amount of LYZ was 5-fold higher than that of BSA, the recovery of BSA reached 75.0%. To prove its practicability, MAIN was successfully employed for the enrichment of histidine-tagged RSV-F0 from the cell culture medium supernatant. According to the optimized conditions, MAIN could enrich approximately 0.1 mg of RSV-F0 from 1 mL of complex biological sample. Therefore, we believe that the novel MAIN could be applicable for efficient separation and purification of His-proteins from complex biological systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Guanidinoacetic acid (GAA) is an amino acid derivative, previously described in the skeletal muscle of vertebrates, that serves as an important regulator of cellular bioenergetics and has been widely used as a feed additive. Nevertheless, the effect of GAA on adipose tissue growth remains unclear. Here, we hypothesized that dietary GAA negatively affected adipose tissue development in lambs. Lambs were individually fed diets with (0.09%) or without GAA for 70 d ad libitum, and the subcutaneous adipose tissues were sampled for analysis. The results showed that dietary GAA supplementation decreased the girth rib (GR) value ( p < 0.01) of lamb carcasses. Both real-time PCR and Western blot analysis suggested that dietary GAA inhibited the expression of adipogenic markers, including peroxisome proliferator-activated receptor γ (PPARγ, p < 0.05), CCAAT/enhancer-binding protein α (C/EBPα, p < 0.01) and sterol-regulatory-element-binding protein 1c (SREBP1C, p < 0.01) in subcutaneous adipose tissue. In vitro, GAA inhibited sheep stromal vascular fraction (SVF) cell proliferation, which was associated with downregulation of proliferating cell nuclear antigen (PCNA, p < 0.05), cyclin-dependent kinase 4 (CDK 4, p < 0.05) and cyclin D1 ( p < 0.01). GAA suppressed adipogenesis of SVF cells. Furthermore, miRNA sequencing revealed that GAA affected the miRNA expression profile, and real-time PCR analysis confirmed that miR-133a expression in both subcutaneous adipose tissue and SVF cell was downregulated by GAA. Meanwhile, miR-133a promoted adipogenic differentiation of SVF cells by targeting Sirt1 . miR-133a mimics alleviated the inhibitory effect of GAA on SVF cells' adipogenic differentiation. In summary, GAA attenuated adipogenesis of sheep SVF cells, which might occur through miR-133a-modulated Sirt1 expression.

Fatty liver disease (FLD) is one of the major causes of chronic liver disease worldwide. With the increasing incidence of obesity and metabolic syndrome worldwide, FLD concomitant with other liver diseases is becoming more common, and multiple etiological overlap is associated with poor disease prognosis. Therefore, FLD concomitant with other liver diseases is a clinical concerning issue. Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease continuum from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), and relative end stage liver disease, excluding other factors that may lead to fatty liver disease such as excessive alcohol consumption et. al. Following the nomenclature of NAFLD with metabolic associated fatty liver disease (MAFLD), an international panel of experts proposed a new name in June 2023 as Metabolic dysfunction - associated steatotic liver disease (MASLD), replacing the word "fatty" with "steatotic," The effect of lipid toxicity on FLD progression was highlighted. Compared with the concept of MAFLD, the disease spectrum of MASLD is broader, and the etiology and mechanism are more clear. The nomenclature of FLD brings some influence to the diagnosis and treatment of chronic liver diseases concomitant with FLD, including chronic hepatitis B, alcoholic fatty liver disease and genetic metabolic diseases. This article reviews the influence of renaming FLD on the diagnosis and treatment of FLD concomitant with other etiologies caused liver diseases.

Objective: We aimed to examine the influence of sleep disturbances on the risk of oligo/astheno/teratozoospermia (OAT) in men attending an infertility clinic., Methods: We consecutively enrolled men attending an infertility clinic from July 2020 to June 2021. Semen parameters were obtained at initial presentation, and the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale score, and the STOP-BANG Questionnair were completed to assess sleep quality. Embryo outcomes were evaluated after infertility treatment., Results: Of 466 men enrolled, 119 had OAT (OAT group) and 347 had normozoospermia (NS group). There were no differences between the two groups regarding Epworth Sleepiness Scale and STOP-BANG Questionnaire scores. The prevalence of poor sleep quality (Pittsburgh Sleep Quality Index score ≥ 5) in the OAT group was significantly higher than that in the NS group (42% vs. 29%, p = 0.009). A higher rate of poor subjective sleep quality was observed in the OAT group compared with the NS group (p = 0.005) and Pearson's correlations revealed a negative relationship between subjective sleep quality and semen quality. Logistic regression found that subjective sleep quality was independently associated with an increased risk of OAT (adjusted odds ratio = 0.610, p = 0.007)., Conclusions: Men with OAT attending an infertility clinic exhibited poor subjective sleep quality. Improving sleep disturbances may be a target intervention to reduce the risk of OAT. This possibility warrants further investigation., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Nanozyme, with enzyme-mimicking activity and excellent stability, has attracted extensive attention. However, some inherent disadvantages, including poor dispersion, low selectivity, and insufficient peroxidase-like activity, still limit its further development. Therefore, an innovative bioconjugation of a nanozyme and natural enzyme was conducted. In the presence of graphene oxide (GO), histidine magnetic nanoparticles (H-Fe 3 O 4 ) were first synthesized by a solvothermal method. The GO-supported H-Fe 3 O 4 (GO@H-Fe 3 O 4 ) exhibited superior dispersity and biocompatibility because GO was the carrier and possessed outstanding peroxidase-like activity because of the introduction of histidine. Furthermore, the mechanism of the peroxidase-like activity of GO@H-Fe 3 O 4 was the generation of •OH. Uric acid oxidase (UAO) was selected as the model natural enzyme and covalently linked to GO@H-Fe 3 O 4 with hydrophilic poly(ethylene glycol) as a linker. UAO could specifically catalyze the oxidation of uric acid (UA) to generate H 2 O 2 , and subsequently, the newly produced H 2 O 2 oxidized the colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue ox-TMB under the catalysis of GO@H-Fe 3 O 4 . Based on the above cascade reaction, the GO@H-Fe 3 O 4 -linked UAO (GHFU) and GO@H-Fe 3 O 4 -linked ChOx (GHFC) were used for the detection of UA in serum samples and cholesterol (CS) in milk, respectively. The method based on GHFU exhibited a wide detection range (5-800 μM) and a low detection limit (1.5 μM) for UA, and the method based on GHFC exhibited a wide detection range (4-400 μM) and a low detection limit (1.13 μM) for CS. These results demonstrated that the proposed strategy had great potential in the field of clinical detection and food safety., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To compare the clinical and pathological features of children with chronic viral hepatitis B combined with metabolic-associated fatty liver disease (CHB-MAFLD) and chronic viral hepatitis B alone (CHB alone), and to further explore the effect of MAFLD on the progression of hepatic fibrosis in CHB. Methods: 701 initially treated CHB children confirmed by liver biopsy admitted to the Fifth Medical Center of the PLA General Hospital from January 2010 to December 2021 were collected continuously. They were divided into CHB-MAFLD and CHB-alone groups according to whether they were combined with MAFLD. A retrospective case-control study was conducted. CHB-MAFLD was used as the case group, and 1:2 propensity score matching was performed with the CHB alone group according to age and gender, including 56 cases in the CHB-MAFLD group and 112 cases in the CHB alone group. The body mass index (BMI), metabolic complications, laboratory indicators, and pathological characteristics of liver tissue were compared between the two groups. The related factors affecting liver disease progression in CHB were analyzed by a binary logistic regression model. The measurement data between groups were compared using the t -test and rank sum test. The χ (2) test was used for the comparison of categorical data between groups. Results: Alanine aminotransferase (ALT, P = 0.032) and aspartate aminotransferase (AST, P = 0.003) levels were lower in the CHB-MAFLD group than those in the CHB alone group, while BMI ( P < 0.001), triglyceride (TG, P < 0.001), total cholesterol ( P = 0.016) and the incidence of metabolic syndrome ( P < 0.001) were higher in the CHB alone group. There were no statistically significant differences in HBsAg quantification or HBV DNA load between the two groups ( P > 0.05). Histologically, the proportion of significant liver fibrosis (S2-S4) was higher in the CHB-MAFLD group than that in the CHB alone group (67.9% vs. 49.1%, χ (2) = 5.311, P = 0.021). Multivariate regression results showed that BMI ( OR = 1.258, 95% CI : 1.145 ~ 1.381, P = 0.001) and TG ( OR = 12.334, 95% CI : 3.973 ~ 38.286, P < 0.001) were the risk factors for hepatic steatosis occurrence in children with CHB. MAFLD ( OR = 4.104, 95% CI : 1.703 ~ 9.889, P = 0.002), liver inflammation ( OR = 3.557, 95% CI : 1.553 ~ 8.144, P = 0.003), and γ-glutamyl transferase ( OR = 1.019, 95% CI : 1.001 to 1.038, P = 0.038) were independent risk factors for significant hepatic fibrosis in children with CH. Conclusion: MAFLD occurrence is related to metabolic factors in children with CHB. Additionally, the combination of MAFLD may promote liver fibrosis progression in CHB patients.

Objectives: Non-alcoholic fatty liver disease (NAFLD) is becoming the leading cause of chronic liver disease worldwide. However, treatment of NAFLD is potentially influenced by psychological conditions. Using the simplified version of the University of Rhode Island Change Assessment (URICA-SV) scale, this study aimed to evaluate the stage of psychological change as a prerequisite to refining implementation strategies for psychological change., Design: A multicentre cross-sectional survey., Setting: Ninety hospitals in China., Participants: 5181 patients with NAFLD were included in this study., Outcome Measures: All patients completed the URICA-SV questionnaire and were assigned to one of the three stages of change (precontemplation, contemplation or action) according to their readiness scores. A stepwise multivariate logistic regression analysis was used to identify independent factors associated with the stage of psychological change., Results: A total of 4832 (93.3%) patients were included in the precontemplation stage and only 349 (6.7%) considered making a change or preparing to make one. There were significant differences in gender (Cohen's d=0.039, p=0.005), age (Cohen's d=-0.327, p<0.001), waist circumference (Cohen's d=0.143, p=0.003), alanine transaminase (Cohen's d=0.347, p=0.001), triglyceride (Cohen's d=0.351, p=0.002), body mass index (BMI; Cohen's d=0.056, p<0.001), proportion of hyperlipidaemia (Cohen's d=0.068, p<0.001) and cardiovascular disease (Cohen's d=0.032, p=0.029), therapeutic regimen (Cohen's d=0.136, p<0.001), and Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease overall score (Cohen's d=-0.420, p<0.001) between patients with NAFLD in the precontemplation stage and those in the contemplation/action stage. Logistic regression identified BMI (HR 0.659, 95% CI 0.469 to 0.928, p=0.017), cardiovascular disease (HR 2.161, 95% CI 1.089 to 4.287, p=0.027) and triglyceride (HR 0.751, 95% CI 0.591 to 0.955, p=0.020) as independent factors predicting psychological change., Conclusions: The results demonstrated that very few patients with NAFLD presented psychological condition in the stage of action. Psychological condition was found to be significantly related to BMI, cardiovascular disease and triglyceride factors. Integrated diversity considerations for evaluating psychological change are necessary., Competing Interests: Competing interests: HR has received speaking fees from Bristol Myers Squibb, Gilead and AbbVie. LW has received research support and/or consulting fees from AbbVie, Bristol Myers Squibb, Gilead, Roche and Novartis., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To explore carnosine dipeptidase 1 (CNDP1) potential value as a diagnostic and prognostic evaluator of hepatocellular carcinoma (HCC). Methods: A gene chip and GO analysis were used to screen the candidate marker molecule CNDP1 for HCC diagnosis. 125 cases of HCC cancer tissues, 85 cases of paracancerous tissues, 125 cases of liver cirrhosis tissues, 32 cases of relatively normal liver tissue at the extreme end of hepatic hemangioma, 66 cases from serum samples of HCC, and 82 cases of non-HCC were collected. Real-time fluorescent quantitative PCR, immunohistochemistry, western blot, and enzyme-linked immunosorbent assay were used to detect the differences in mRNA and protein expression levels of CNDP1 in HCC tissue and serum. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival were used to analyze and evaluate the value of CNDP1 in the diagnosis and prognosis of HCC patients. Results: The expression level of CNDP1 was significantly reduced in HCC cancer tissues. The levels of CNDP1 were significantly lower in the cancer tissues and serum of HCC patients than those in liver cirrhosis patients and normal controls. ROC curve analysis showed that the area under the curve of serum CNDP1 in the diagnosis of HCC patients was 0.753 2 (95% CI 0.676-0.830 5), and the sensitivity and specificity were 78.79% and 62.5%, respectively. The combined detection of serum CNDP1 and serum alpha-fetoprotein (AFP) significantly improved the diagnostic accuracy (AUC = 0.820 6, 95% CI 0.753 5-0.887 8). The diagnostic sensitivity and specificity of serum CNDP1 for AFP-negative HCC patients were 73.68% and 68.75% (AUC = 0.793 1, 95% CI 0.708 8-0.877 4), respectively. In addition, the level of serum CNDP1 distinguished small liver cancer (tumor diameter < 3 cm) (AUC = 0.757 1, 95% CI 0.637 4-0.876 8). Kaplan-Meier survival analysis showed that CNDP1 was associated with a poor prognosis in HCC patients. Conclusion: CNDP1 may be a potential biomarker for the diagnostic and prognostic evaluation of HCC, and it has certain complementarity with serum AFP.

Background and Objective : This meta-analysis was performed to compare the effectiveness of surgical treatment and conservative treatment in adult ankle fractures. Methods : Pubmed, Embase, and Cochrane-Library databases were searched to retrieve prospective randomized-controlled studies that compared the efficacy of surgical treatment and conservative treatment in adult ankle fractures. The meta package in R language was used to organize and analyze the obtained data. Results : A total of eight studies involving 2081 patients was considered eligible, including 1029 patients receiving surgical treatment and 1052 receiving conservative treatment. This systematic review and meta-analysis was prospectively registered on PROSPERO, and the registration number is CRD42018520164. Olerud and Molander ankle-fracture scores (OMAS) and the health survey 12-item Short-Form (SF-12) were used as main outcome indicators, and the follow-up outcomes were grouped according to the follow-up time. Meta-analysis results showed significantly higher OMAS scores in patients receiving surgical treatment than those with conservative treatment at six months (MD = 1.50, 95% CI: 1.07; 1.93) and over 24 months (MD = 3.10, 95% CI: 2.46; 3.74), while this statistical significance was absent at 12-24 months (MD = 0.08, 95% CI: -5.80; 5.96). At six months and 12 months after treatment, patients receiving surgical treatment exhibited significantly higher SF12-physical results than those receiving conservative treatment (MD = 2.40, 95% CI: 1.89; 2.91). The MD of SF12-mental data at six months after meta-analysis was -0.81 (95% CI: -1.22; 0.39), and the MD of SF12-mental data at 12+ months was -0.81 (95% CI: -1.22; 0.39). There was no significant difference in SF12-mental results between the two treatment methods after six months, but after 12 months, the SF12-mental results of patients receiving surgical treatment were significantly lower than those of conservative treatment. Conclusions : In the treatment of adult ankle fractures, surgical treatment is more efficacious than conservative treatment in improving early and long-term joint function and physical health of patients, but it is associated with long-term adverse mental health.

Objectives: To study the role and mechanism of platelet-derived growth factor BB (PDGF-BB) on platelet production in Kawasaki disease (KD) mice and human megakaryocytic Dami cells through in vitro and in vivo experiments., Methods: ELISA was used to measure the expression of PDGF in the serum of 40 children with KD and 40 healthy children. C57BL/6 mice were used to establish a model of KD and were then randomly divided into a normal group, a KD group, and an imatinib group (30 mice in each group). Routine blood test was performed for each group, and the expression of PDGF-BB, megakaryocyte colony forming unit (CFU-MK), and the megakaryocyte marker CD41 were measured. CCK-8, flow cytometry, quantitative real-time PCR, and Western blot were used to analyze the role and mechanism of PDGF-BB in platelet production in Dami cells., Results: PDGF-BB was highly expressed in the serum of KD children ( P <0.001). The KD group had a higher expression level of PDGF-BB in serum ( P <0.05) and significant increases in the expression of CFU-MK and CD41 ( P <0.001), and the imatinib group had significant reductions in the expression of CFU-MK and CD41 ( P <0.001). In vitro experiments showed that PDGF-BB promoted Dami cell proliferation, platelet production, mRNA expression of PDGFR-β, and protein expression of p-Akt ( P <0.05). Compared with the PDGF-BB group, the combination group (PDGF-BB 25 ng/mL + imatinib 20 μmol/L) had significantly lower levels of platelet production, mRNA expression of PDGFR-β, and protein expression of p-Akt ( P <0.05)., Conclusions: PDGF-BB may promote megakaryocyte proliferation, differentiation, and platelet production by binding to PDGFR-β and activating the PI3K/Akt pathway, and the PDGFR-β inhibitor imatinib can reduce platelet production, which provides a new strategy for the treatment of thrombocytosis in KD.

Determination of trace glycoprotein has important guiding significance in clinical diagnosis and is usually achieved by immunoaffinity. However, immunoaffinity possesses inherent drawbacks, such as poor probability of high-quality antibodies, instability of biological reagents, and harmfulness of chemical labels to the body. Herein, we propose an innovative method of peptide-oriented surface imprinting to fabricate artificial antibody for recognition of glycoprotein. By integrating peptide-oriented surface imprinting and PEGylation, an innovative hydrophilic peptide-oriented surface imprinting magnetic nanoparticle (HPIMN) was successfully fabricated with human epidermal growth factor receptor-2 (HER2) as a model glycoprotein template. In addition, we further prepared a novel boronic acid-modified/fluorescein isothiocyanate-loaded/polyethylene glycol-covered carbon nanotube (BFPCN) as fluorescence signal output device, which was loaded with numerous fluorescent molecules could specifically label the cis-diol of glycoprotein at physiological pH via boronate-affinity interaction. To prove the practicability, we proposed a HPIMN-BFPCN strategy, in which the HPIMN first selectively captured the HER2 due to the molecular imprinted recognition and then the BFPCN specific labeled the exposed cis-diol of HER2 based on the boronate-affinity reaction. The HPIMN-BFPCN strategy exhibited ultrahigh sensitivity with limit of detection of 14 fg mL -1 and was successfully used in the determination of HER2 in spiked sample with recovery and relative standard deviation in the range of 99.0%-103.0% and 3.1%-5.6%, respectively. Therefore, we believe that the novel peptide-oriented surface imprinting has great potential to become an universal strategy for fabrication of recognition units for other protein biomarkers, and the synergy sandwich assay could become a powerful tool in prognosis evaluation and clinical diagnosis of glycoprotein-related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Hepatitis type E virus (HEV) is one of the main causes of acute hepatitis globally and has thus gained attention as a public health issue. The diverse clinical manifestations of hepatitis type E are typically acute and self-limiting with mild symptoms, but populations with underlying liver disease or immunocompromised patients can have severe and chronic symptoms. Severity and chronicity can arise and manifest as fulminant hepatitis, chronic hepatitis, or even hepatic failure. HEV infection-induced hepatic failure (acute-on-chronic liver failure), based on the different backgrounds of chronic liver disease, is a clinical phenotype of severe HEV infection that requires attention. In addition, HEV infection can exhibit extrahepatic clinical manifestations of multi-system and organ involvement like neurological diseases (Guillain-Barré syndrome), renal diseases (membranous/membranous proliferative glomerulonephritis, cryoglobulinemia), and blood diseases (thrombocytopenia). At home or abroad, there are no antiviral drugs approved, particularly for HE treatment. Since most acute HE can resolve spontaneously, no special treatment is required clinically. However, in patients with severe or chronic HE, ribavirin (RBV) monotherapy and/or pegylated interferon-combination therapy have achieved certain antiviral effects. Combined small-molecule drugs and RBV have been attempted to treat HEV, but high-level evidence-based treatment is still lacking. Thus, new, highly effective anti-HEV drugs are clinical priorities to address these concerns. Severe and chronic HEV infections' clinical phenotype, early detection, mechanism, intervention, and outcome need additional study.

Background: Although metaphyseal ulnar shortening osteotomy (MUSO) is safer for the treatment of ulnar impaction syndrome (UIS) than diaphyseal ulnar shortening osteotomy (DUSO), DUSO is widely used for UIS treatment., Aim: To evaluate the effectiveness of DUSO and MUSO for UIS treatment and determine the factors that should be considered when choosing surgical treatment for UIS., Methods: Articles comparing the effectiveness of DUSO and MUSO for UIS treatment were systematically retrieved from MEDLINE (Ovid), PubMed, EMBASE, and Cochrane Library. The demography, incidence of complications, secondary operation rate, postoperative DASH score, wrist pain on the visual analogue scale, and grip strength improvement were also evaluated. In addition, the correlation between the improvement of grip strength and the shortening of osteotomy length of ulna was analyzed. The outcome of the patient was discontinuous, and the odds ratio, risk ratio (RR), and 95%CI were calculated and analyzed via RevMan5.3 software., Results: Six studies, including 83 patients receiving MUSO (experimental group) and 112 patients receiving DUSO (control group), were included in the meta-analysis. The second operation rate was significantly higher after DUSO than after MUSO. The DASH scores were slightly lower in the MUSO group than in the DUSO group. The patients receiving MUSO had slightly better pain relief effect than patients receiving DUSO. However, the incidence of complications and improvement of grip strength were not significantly different between the two groups., Conclusion: Although DUSO and MUSO provide similar effects for UIS, MUSO is associated with a lower secondary operation rate, slightly lower postoperative DASH scores and slightly better pain relief effect than DUSO, indicating that MUSO can effectively be used for UIS treatment., Competing Interests: Conflict-of-interest statement: There is no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Liver histological assessment is of great clinical significance for the diagnosis, classification, and prognosis prediction of drug-induced liver injury (DILI). Liver histological evaluation can effectively supplement RUCAM. The clinical phenotypes of DILI are complex and diverse, including acute, chronic and severe hepatic injury. DILI has multiple insult-targets, including hepatocytes, cholangiocytes, and vascular endothelial cells and others. The pathological damage patterns are similar to many types of non-DILI liver diseases, therefore making differential diagnosis difficult. New anti-tumor drugs such as immune checkpoints inhibitors and targeted therapy are widely used in clinical antineoplastic practice, thus the growing incidence of related liver injury occurs. Liver histological examination can effectively assess the pathological phenotypes and severity of DILI, so as to guide treatment. In uncommon conditions such as special types of DILI (such as hepatic vascular disease), DILI with other competitive etiology overlapping, chronic DILI, and DILI induced liver failure, liver histological assessment can provide strong support for identifying the cause, rational treatment, and prognosis. Currently, the histological evaluation system for drug-induced liver injury seems to be a lack of consensus, and the diagnosis of DILI is short of highly specific and sensitive serological markers. All in all, liver histological assessment plays a crucial role in the diagnosis and differential diagnosis of DILI.